A5001307090- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Diabetes and associated disorders
- Cancer-related molecular mechanisms research
- Dietary Effects on Health
- Adipokines, Inflammation, and Metabolic Diseases
- Galectins and Cancer Biology
- Lipid metabolism and disorders
- Asthma and respiratory diseases
- MicroRNA in disease regulation
- T-cell and Retrovirus Studies
- Lymphoma Diagnosis and Treatment
- Pediatric health and respiratory diseases
- Gut microbiota and health
- Diet, Metabolism, and Disease
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Salivary Gland Disorders and Functions
- Cell Adhesion Molecules Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Glycosylation and Glycoproteins Research
VA Eastern Colorado Health Care System
2023-2024
United States Department of Veterans Affairs
2023-2024
Weiss Memorial Hospital
2024
University of Colorado Anschutz Medical Campus
2019-2023
University of Colorado Denver
2014-2023
Rocky Mountain MS Center
2022
Cincinnati Children's Hospital Medical Center
2009-2021
University of Cincinnati Medical Center
2009-2021
University of Cincinnati
2009-2013
Oklahoma Medical Research Foundation
2002-2010
Inflammation plays a central pathogenic role in the pernicious metabolic and end-organ sequelae of obesity. Among these sequelae, nonalcoholic fatty liver disease (NAFLD) has become most common chronic developed world. The twinned observations that obesity is associated with increased activation interleukin (IL)-17 axis this can regulate damage diverse contexts prompted us to address IL-17RA signaling progression NAFLD. We further examined whether microbe-driven IL-17A regulated NAFLD...
Non-alcoholic fatty liver disease (NAFLD) is a common chronic illness with genetically heterogeneous background that can be accompanied by considerable morbidity and attendant health care costs. The pathogenesis progression of NAFLD complex many unanswered questions. We conducted genome-wide association studies (GWASs) using both adult pediatric participants from the Electronic Medical Records Genomics (eMERGE) Network to identify novel genetic contributors this condition.First, natural...
Abstract Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element will advance human mechanisms. Here, we report systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption a element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure show tags cell-type dependent distal enhancer specific physically...
The gut microbiome has been proposed to play a causal role in obesity. Here, we review the historical context for this hypothesis, highlight recent key findings, and critically discuss issues central further progress field, including epistemological problem field: how define causality relationship between microbiota obesity phenotypes. Definition of such will be critical field move forward.
Osteopontin (SPP1) is an important bone matrix mediator found to have key roles in inflammation and immunity. SPP1 genetic polymorphisms increased osteopontin protein levels been reported be associated with SLE small patient collections. The present study evaluates association between a large cohort of 1141 unrelated patients [707 European-American (EA) 434 African-American (AA)], 2009 controls (1309 EA 700 AA). Population-based case-control analyses were performed. To control for potential...
Preterm birth (PTB) is a leading worldwide cause of morbidity and mortality in infants. Maternal inflammation induced by microbial infection critical predisposing factor for PTB. However, biological processes associated with competency pathogens, including viruses, to induce PTB or sensitize secondary bacterial infection-driven are unknown. We show that pathogen/pathogen-associated molecular pattern-driven activation type I IFN/IFN receptor (IFNAR) was sufficient prime systemic uterine...
Background: CXorf21 and SLC15a4 both contain risk alleles for systemic lupus erythematosus (SLE) Sjögren's syndrome (pSS). The former escapes X inactivation. Our group predicts specific endolysosomal-dependent immune responses are driven by the protein products of these genes, which form a complex at endolysosomal surface. previous studies have shown that knocking out increases lysosomal pH in female monocytes, present study assesses whether 46,XX women, who overexpress B cells dendritic...
Background: Ninety percent of systemic lupus erythematosus (SLE) patients are women. X chromosome-dosage increases susceptibility to SLE and primary Sjögren's Syndrome (pSS). Chromosome open reading frame 21 (CXorf21) escapes X-inactivation is an risk gene previously unknown function. We undertook the present study delineate function CXorf21 in immune system as well investigate a potential role sex bias pSS. Methods: Western blot protein analysis, qPCR, BioPlex cytokine immunoassay, pHrodo™...
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa IFN expressed in A pooled genome-wide scan implicated IFNK locus SLE susceptibility. We studied single nucleotide polymorphisms (SNPs) 3982 cases 4275 controls, composed of European (EA), African-American (AA), Asian ancestry. rs12553951C was associated with EA males (<mml:math...
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well environmental factors. We undertook to study the role of TRAF6 candidate gene for SLE, since it plays major in several signaling pathways that are important immunity and organ development.Fifteen single-nucleotide polymorphisms (SNPs) across were evaluated 7,490 SLE patients 6,780 control subjects different ancestries....
Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently sclerosis. While is involved trafficking of epidermal growth factor Receptor (EGFR) COS-7 cells, mechanisms linking to pathophysiology remained undefined. In an effort uncover the mechanism at this locus increases lupus-risk, we undertook a fine-mapping analysis large multi-ancestral...
Aim Prolidase deficiency is a rare autosomal recessive disease in which one of the last steps collagen metabolism, cleavage proline-containing dipeptides, impaired. Only about 93 patients have been reported with 10% also having systemic lupus erythematosus (SLE). Methods We studied large extended Amish pedigree four prolidase and three heterozygous individuals for lupus-associated autoimmunity. Eight unaffected children served as normal controls. genetics enzyme activity were confirmed....
Abstract The impact of immune mediators on weight homeostasis remains underdefined. Interrogation resistance to diet-induced obesity in mice lacking a negative regulator Toll-like receptor signaling serendipitously uncovered role for B cell activating factor (BAFF). Here we show that overexpression BAFF multiple mouse models associates with protection from gain, approximating log-linear dose response relation concentrations. Gene expression analysis BAFF-stimulated subcutaneous white...
Alterations in the gut microbiota have been proposed to modify development and maintenance of obesity its sequelae. Definition underlying mechanisms has lagged, although ability commensal microbes drive pathways involved inflammation metabolism generated compelling, testable hypotheses. We studied C57BL/6 mice from two vendors that differ their obesogenic response colonization by specific members having well-described roles regulating immune responses. confirmed presence robust differences...
To explore the potential influence of polymorphic 8p23.1 inversion on known autoimmune susceptibility risk at or near BLK locus, we validated a new bioinformatics method that utilizes SNP data to enable accurate, high-throughput genotyping in Caucasian population. Methods: Principal components analysis (PCA) was performed using markers inside territory followed by k-means cluster analyses 7416 European derived and 267 HapMaP CEU TSI samples. A logistic regression conditional performed....
The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation p53 tumor suppressor pathway. Presence this single nucleotide (SNP) has been associated with earlier tumorigenesis patients Li-Fraumeni syndrome, as well decreased survival CLL. In addition, cells homozygous (G/G) for SNP 309 were found have 10-fold increase resistance topoisomerase II inhibitors vitro.We genotyped children (n = 575) de novo acute myeloid leukemia (AML)...